The field of this invention is a disease condition selected from the group consisting of multiple sclerosis (including the various forms and stages of multiple sclerosis), a humoral immune response that may accompany multiple sclerosis (a xe2x80x9cpro-MS immune responsexe2x80x9d), and a combination thereof.
Multiple sclerosis (xe2x80x9cMSxe2x80x9d) is a chronic inflammatory disease of the central nervous system. The characteristic pathological feature, and still used as the primary basis for diagnosis of MS, is demyelination of the myelin sheath of neurons in the central nervous system. MS affects 250,000 to 350,000 in the United States, and approximately 1 million people worldwide. Typically, MS begins as a relapsing-remitting disease (RRMS) with periodic episodes of associated symptoms (e.g. various forms of neuritis). Often RRMS eventually changes to a progressive course of disease, secondary progressive MS (SPMS), characterized by more inflammation than RRMS or primary progressive MS, and hence, more CNS tissue damage which results in more debilitating symptoms. However, in 10 to 20% of individuals, the disease initially develops in a progressive form known as primary progressive MS (PPMS).
There is clear understanding of the immunopathogenic processes associated with MS; and, to date, their lacks evidence of a unique immunologic abnormality in individuals with MS (Whitaker, 1998, N. Engl. J. Med. 339:339-340; Rudick et al., 1997, N. Engl. J. Med. 337:1604-1611). Because of the incomplete understanding of the pathogenesis of MS, therapeutic advances have been slow to emerge. The myelin sheath and oligodendrocytes are believed to be main targets of autoreactive T cells which, when activated and reach the central nervous system (CNS), are thought to secrete proinflammatory cytokines. These cytokines are believed to induce astrocytes and leukocytes (including by activating microglia and macrophages) to secrete enzymes which damage myelin, and result in inflammation, demyelination, and axonal damage in the central nervous system characteristic in MS. Thus, studies have implicated a cell-mediated immune response, involving T cells recognizing epitopes of myelin basic protein (MBP), in the pathogenesis of MS.
Currently, the characterization of disease condition related to MS (including diagnosis, staging, monitoring disease progression, monitoring treatment effects on disease activity, and the like) is imprecise. Imaging that detects what appears to be plaques in CNS tissue is typically insufficient, by itself, to give a definitive diagnosis of MS. Often, diagnosis of MS is made only after both detection of plaques and of clinically evident neuropathy. It is clear that diagnosis of MS is usually made well after initiation of the disease process; i.e., only after detection of a sufficient number of plaques and of clinically evident neurological symptoms. Additionally, staging of MS is typically done by subjective measurements of exacerbation of symptoms, as well of other clinical manifestations. There are difficulties in diagnosis and staging because symptoms vary widely among individuals and change frequently within the individual. Thus, there is the need for tests which can aid in the diagnosis and staging of MS. Further, presently there are no commercially available tests to evaluate for the presence of a pro-MS immune response. There is a need for laboratory tests that distinguish individuals who are more likely to have a favorable prognosis (e.g., one or more of stable remission; limited, localized disease progression; response to anti-MS therapy that either stabilizes or reduces the rate of disease progression) from individuals who are likely to have an unfavorable prognosis (e.g., individuals having undergone anti-MS therapy but who still have indications of a pro-MS immune response, and are thus still at risk for progression of the disease process; individuals having both clinically evident MS and a pro-MS immune response). Additionally, there is a need for markers that can be used as indicators for predicting whether a particular therapeutic (e.g., drug or immunotherapeutic) can effectively reduce a pro-MS immune response. Recently, one skilled in the field of MS summarized the need: xe2x80x9cThe need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized.xe2x80x9d
Therefore, a need exists for compositions and methods which may be used to characterize a disease condition selected from the group consisting of MS, a pro-MS immune response, and a combination thereof.
It is suggested that MS may actually be different diseases of similar pathology which are lumped together. According to a primary object of the present invention, provided are markers which may be determined by analyzing a body fluid of an individual having a disease condition selected from the group consisting of MS, a pro-MS immune response, and a combination thereof; wherein the markers differ in the disease condition as compared to reference values for the respective markers established from apparently healthy individuals.
In another object, one or more markers may be an indicator for a form or forms of the disease condition; may also be used to stage the development or progression of the disease condition; and may be used to monitor treatment of the disease condition.
In another object, provided are methods for assaying a clinical sample for the one or more markers. Also provided are assay kits for use in detecting or detecting and quantitating (individually or collectively referred to hereinafter as determining) an amount of the one or more markers in practicing the methods according to the present invention.
In another object provided are detection of sialocomplexes, and methods of removing sialocomplexes from a body fluid of an individual having a disease condition selected from the group consisting of MS, a pro-MS immune response, and a combination thereof.
The above and other objects, features, and advantages of the present invention will be apparent in the following Detailed Description of the Invention, when read in conjunction with the accompanying drawings.